Proteome microarray identifies autoantibody biomarkers for diagnosis of hepatitis B-related hepatocellular carcinoma

Abstract

Background and aimsHepatocellular carcinoma (HCC) has the highest mortality rate among malignant tumors worldwide. This study aimed to analyze the biological characteristics of serum proteins in hepatitis B (HBV)-related liver diseases, identify diagnostic biomarkers for HBV-infected HCC, and provide a scientific basis for its prevention and treatment. Materials and methodsWe used HuProt arrays to identify candidate biomarkers for HBV-related liver diseases and verified the differential biomarkers by using an HCC-focused array. The biological characteristics of serum proteins were analyzed via bioinformatics. Serum biomarkers levels were validated by ELISA. ResultsWe identified 547 differentially expressed proteins from HBV-infected HCC in a screening cohort. After analyzing the biological characteristics of serum proteins, we identified 10 potential differential autoantibodies against tumor-associated antigens (TAAbs) and a candidate biomarker panel (APEX2, RCSD1, and TP53) for the diagnosis of HBV-associated HCC with 61.9% sensitivity and 81.7% specificity in an HCC-focused array validation cohort. Finally, the protein levels and diagnostic capability of the biomarker panel were confirmed in a large-sample validation cohort, and this panel was found to be superior to alpha-fetoprotein, the standard hallmark for the diagnosis of HCC. ConclusionThe APEX2, RCSD1, and TP53 biomarker panels could be used for the diagnosis of HBV-associated HCC, providing a scientific basis for clinical practice.